Phase II study of topotecan in patients with recurrent malignant glioma

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Abstract
Background: The NCIC Clinical Trials Group has an ongoing interest in assessing investigational agents in minimally pretreated patients with malignant glioma. Topotecan is one of the first topoisomerase I inhibitors to enter clinical trials and has shown early evidence of activity in several solid tumors. We have conducted a phase II trial of topotecan in patients with malignant glioma. Methods: Adults with malignant glioma and recurrent contrast enhancing measurable disease (⩾2 × 2 cm) were eligible. Topotecan 1.5 mg/m2 i.v. was given daily × five days every three weeks. Response and toxic effects were assessed at the end of each cycle. Results: Thirty-one patients were entered onto the study: fifteen had glioblastoma, 16 anaplastic astrocytoma, all had prior radiation, 15 prior chemotherapy, and all were assessable for response and toxicity. Two patients (6%) responded: one had a complete radiographic response, but died with neutropenic sepsis, and the second had a prolonged partial response (> 97 weeks). Twenty-one patients (68%) had stable disease for five to 86+ weeks (median 19) and eight (26%) had progressive disease after one cycle. Toxicity was primarily hematologic; 18 (58%) had grade 4 neutropenia (<0.5 × 109/1), usually brief, and three (10%) grade 4 thrombocytopenia (<25 × 109/1). Twelve of 109 cycles (11%) were given at reduced dose. Conclusions: Topotecan in this dose and schedule has only modest activity in recurrent glioblastoma and anaplastic astrocytoma.